We propose to acquire an upright, multiphoton and confocal microscope to support the research of investigators at the University of Maryland in the School of Medicine, Dental School, School of Nursing, and Comprehensive Cancer Center. The investigators selected as Major Users, like many at the University, have immediate need for fluorescence imaging deep within intact or in vivo systems. However, they are currently limited in their ability to accomplish key aims of their research using only confocal microscopy, which penetrates only to shallow layers. Multiphoton microscopes represent the current standard configuration for in vivo and thick-tissue high-resolution imaging in universities around the world However, no equipment with the required capabilities is available to the users, and indeed no upright multiphoton microscope is present within the entire University of Maryland Baltimore campus. This has left a debilitating hole in our ability to conduct relevant research in many of our key areas, and the proposed microscope is designed to remedy this problem. During a series of on-campus demos involving microscopes from three major manufacturers, the Major Users collected substantial preliminary data, and each confirmed that the capabilities of the Zeiss 710NLO directly met their requirements. Zeiss supplies a number of multiphoton microscope configurations, but the 710NLO provides an excellent combination of capabilities: high-sensitivity detectors for time-lapse imaging in thick and scattering tissues; compact light path for preserving laser power and beam quality on the illumination side and conserving photons on the emission side; spectral detection for removal of autofluorescence; high ease of use due to familiarity with Zeiss software; an excellent new upright microscope design optimized for patch-clamp electrophysiology; dependable local service; as well as a top-quality pulsed laser tunable over a broad wavelength for diverse projects. The new instrument will be incorporated into the long-standing and successful Confocal Core Facility at the University. The presence of extensive on-campus expertise along with pledged support from experts at nearby institutions, promise swift and efficient utilization of the microscope. Funded by a major NCRR construction grant, the Core is currently undergoing extensive renovations to house our confocal microscopes. The system matches the long-term goals of the Deans of the School of Medicine, School of Nursing, and Dental School to build research resources, and accordingly, institutional support is very strong. The availability of the LSM710 NLO in the School's Confocal Core Facility would directly and strongly benefit the research of the Major Users. More broadly, it will add critically important new capabilities to advance NIH-sponsored research throughout a large and diverse medical research university. PUBLIC HEALTH RELEVANCE: The University of Maryland has established itself as an international leader in the area of biological microscopy. The instrument requested in this proposal will be used to explore new directions in our traditional areas of strength, including cardiology, neuroscience, hypertension, cancer biology, and diabetes. By permitting visualization of cellular- and organ-level structure and function within the most intact systems possible-including within living animals- this microscope will immediately and dramatically advance our efforts to bring life sciences research to bear on human health.